AB0170 AMCV POSITIVITY AND HIGHER SERUM IP-10 (CXCL-10) LEVEL ARE ASSOCIATED WITH A MORE PRONOUNCED EFFECT OF ABATACEPT THERAPY
Authors: M. Borisova, G. Lukina, Y. Sigidin, E. Luchikhina, D. Karateev, A. Novikov, E. Aleksandrova, M. Cherkasova, E. Aronova, S. Glukhova, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2022)

Background With the advent of medications with different mechanisms of action in the treatment of rheumatoid arthritis (RA), clinicians face the challenge of personalizing the approach to the treatment of RA patients. One of the steps in this direction is to identify predictors of the effectiveness of the therapy. This work is devoted to the identification of predictors of the therapy effectiveness with the blocker of T cells co-stimulation - abatacept (ABA). Objectives Search for clinical and immunological predictors of the effectiveness of ABA therapy. Methods 91 patients were included in the study, most of them women, with high disease activity of RA (DAS28=5.1±1.0, SDAI=28±13.4, CDAI=25±12) and failure of previous biologics (51, 6%) and DMARDs (100%). Moreover, in 20% (n=18) of patients the inefficiency more than 2 biologics were recorded. The average duration of the disease was 3.0 (1.4–12) years, most patients were positive for RF 72.5%, ACCP 77%, AMCV 86%. In 44 patients the levels of RF, ACCP, AMCV and MMP-3 were assessed after 24 weeks of ABA therapy. In 36 patients enzyme-linked immunoassay was used to measure serum concentrations of biomarkers IL-1β, IL-6, IL-17AF, TNF-α, VEGF-A, IP-10, YKL-40 at baseline and after 24 weeks of ABA therapy. The effectiveness of therapy was assessed according to the EULAR criteria. ABA IV infusions were performed according to the standard schedule. Methods of parametric and non-parametric statistics were used in statistical analysis. Results ABA treatment led to a significant decrease of disease activity assessed by DAS28, SDAI, CDAI starting from 3 months of therapy (p&lt;0.05). More than half of the patients were in remission and had low disease activity according to the DAS28 (65.7%, n=35) after 48 weeks of treatment. After 48 weeks, the highest percentage of patients with RA remission was registered by the DAS28 (37.4%, n=20), the lowest — SDAI (21.6%, n=11). After 24 weeks of therapy, ABA led to a significant decrease in the serum levels of IL-6 from 2.4 [1.1 - 6,4] to 1.29 [0.9-2.2] pg/ml, (p=0.0006), IP-10 from 21 [12,9-49,8] to 14 [7.5-28] pg/ml, (p=0.007) and matrix metalloproteinase 3 (MMP3) from 30.1 [13-82] pg/ml to 10 [7.4-55] pg/ml, (p = 0.0003). A decrease in the serum level of IL-6 significantly correlated with a decrease in the DAS28 and SDAI (r=0.5 and r=0.479, p&lt;0.05), IP-10 with DAS28 (r=0.326, p&lt;0.05). Initially, the serum level of TNF-α was significantly lower in patients who achieved low disease activity by the SDAI (72.6%, n=37) after 48 weeks of therapy, compared with the rest. On the contrary, a significantly higher level of IP-10 before treatment was recorded in patients with a good response according to the EULAR criteria (39%, n=29) after 48 weeks of ABA treatment (Figure 1). The ROC-analysis revealed that an initially high concentration of TNF-α may indicate with 71% sensitivity and 77% specificity about the possible ineffectiveness of ABA therapy after 48 weeks of treatment, the area under the curve was 0.7, 95% CI (0.5– 0.9). In patients initially positive for AMCV, low RA activity by SDAI was significantly more often registered after 24 (p=0.04) and 48 weeks. (p=0.01). 89% (n=34) of AMCV-positive patients achieved low disease activity after 48 weeks therapy by the SDAI and CDAI. It is noteworthy that a cohort of patients with insufficient effect after 48 weeks consisted entirely of AMCV-negative patients. Conclusion ABA therapy led to a significant decrease in disease activity according to the main indices (DAS28, SDAI, CDAI). During ABA treatment, there was a decrease of important immunoinflammatory markers - IL-6, IP-10, MMP-3. AMCV positivity is significantly associated with higher efficacy of ABA therapy. Also, a high basal concentration of TNF-α could use as a predictor of possible failure of ABA therapy, and a high initial level of IP-10, on the contrary, indicates the possible efficacy of ABA therapy. References None Disclosure of Interests None declared